Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)

Inclusion Criteria: Participants must meet the following criteria on screening examination to be eligible toparticipate in the study:

1. Tumor: Newly diagnosed non-disseminated diffuse intrinsic pontine glioma based onclassic clinical AND radiographic finding.

2. No prior radiation therapy or chemotherapy.

3. Age: Patient must be 3 to < 18 years of age at the time of diagnosis.

4. Performance Score: Karnofsky Performance Scale > 12 y/o >/= 50 or Lansky PerformanceScore for patients < 12y/o 50 assessed within two-weeks prior to enrollment.

5. Participants must have normal organ and marrow function as defined below within twoweek s prior to enrollment:

• Absolute neutrophil count > 1,000/mcL

• Platelets > 100,000/mcL (transfusion independent)

• Hemoglobin > 8gm/dL (can be transfused)

• Hepatic: Total bilirubin < 1.5 times the upper limit of normal; alanineaminotransferase [SGPT (ALT)] and aspartate aminotransferase [SGOT (AST)] < 5times the institutional upper limit of normal.

• Renal: Serum creatinine which is less than 1.5x the upper limit of institutionalnormal for age or Glomerular Filtration Rate (GFR) > 70 ml/min/1.73m2.

6. Female patients of childbearing potential must have negative serum or urine pregnancytest. Patient must not be pregnant or breast feeding.

7. Patients of childbearing or child-fathering potential must be willing to use amedically acceptable form of birth control, which includes abstinence, while beingtreated on this study.

8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients must not have any significant medical illnesses that in the investigator'sopinion cannot be adequately controlled with appropriate therapy or would compromisethe patient's ability to tolerate this therapy.

2. Patients receiving any other anticancer or experimental drug therapy.

3. Patients with disseminated intrinsic diffuse brainstem gliomas in either brain orspine (can be based on clinical evaluation).

4. Participants receiving any medications or substances that are strong/intermediateinhibitors or inducers of Cytochrome P450 (CYP450), Cytochrome P3A4(CYP3A4) orCytochrome 1A2 (CYP1A2) are ineligible. Lists including medications and substancesknown or with the potential to interact with the CYP450 CYP3A4 or CYP1A2 isoenzymesare provided in Appendix I.

5. Use of hematopoietic growth factors within the 2 weeks prior to initiation of therapy.

6. Patients with evidence of spontaneous hemorrhage greater than 0.5cm unrelated tosurgery.

7. Uncontrolled intercurrent illness including, but not limited to ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements.

8. Pregnant women are excluded from this study because bevacizumab, temozolomide anderlotinib can have potential for teratogenic or abortifacient effects. Because thereis an unknown but potential risk of adverse events in nursing infants secondary totreatment of the mother with these agents, breastfeeding should be discontinued.